Ufmylation-Deficient DDRGK1 Ameliorates Obesity by Inhibiting FASN-Mediated Adipocyte Lipogenesis
Li Y., Zhou T., Yang X., Rong K., Cao X., Shi L.
Animal Study with a reported sample of 23, published in Adv Sci (Weinh) (2026) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Adv Sci (Weinh) (2026)
- Reported sample size
- 23
- Source database
- Europe PMC
- PMID
- 41671397
- PMCID
- PMC13073236
- DOI
- 10.1002/advs.202514702
Abstract (original English)
Fatty acid synthase (FASN) is a central regulator of obesity through de novo lipogenesis (DNL), undergoes precise control via the ubiquitin-proteasome system, yet its obesity-related post-translational modifications remain unclear. Our clinical investigation of human adipose tissue (n = 23) demonstrated elevated FASN protein in overweight individuals, mirroring high-fat diet (HFD) mouse models. However, transcriptomic analysis of 770 GEO samples paradoxically revealed inverse correlation between FASN mRNA and BMI. Mechanistically, we identified DDRGK1 as a UFMylation effector that stabilizes FASN by competitively inhibiting ubiquitination. Genetic disruption of this pathway in Ddrgk1 K268R mutant mice conferred metabolic protection, with 12% reduced body weight and 18% decreased fat mass under HFD conditions, alongside improved glucose homeostasis. Single-nucleus RNA sequencing of inguinal white adipose tissue (iWAT) demonstrated reprogrammed metabolic flux in mutant mice, complemented by lipidomic profiling showing attenuated DNL. In vitro studies confirmed that DDRGK1 deficiency impairs adipocyte lipid droplet formation (reversible by palmitate acid supplementation) through FASN destabilization. Our work elucidates the adipocyte-specific DDRGK1-UFMylation-FASN axis as a novel therapeutic target for obesity-associated metabolic dysfunction.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
How we grade evidenceBrowse all related research
Filter the research library by this study's title keywords, author, or publication year.